Merkel cell carcinoma (MCC) is the unsung villain of the skin cancer world – rare, aggressive, and often flying under the radar. MCC is a neuroendocrine skin cancer that usually rears its ugly head as a firm, painless nodule on sun-exposed areas of the skin. Risk factors for this sneaky skin invader include advanced age, fair skin, UV light exposure, immunosuppression, and exposure to the Merkel cell polyomavirus (MCPyV). Diagnosis typically involves a biopsy, and treatment options range from surgery, radiation, and/or immunotherapy and occasionally chemotherapy.
To truly understand the impact of MCC and its treatments, let’s take a look at three unique patient cases I saw this past week:
The Miracle of Immunotherapy: One of the patients I treated with metastatic MCC involving the lymph nodes, lungs, and liver received off-label PD1 inhibitor immunotherapy, achieving a complete and durable remission lasting over 7-8 years. This case highlights the potential for single-agent immunotherapy with drugs like avelumab or pembrolizumab, elicit responses in 40-50% of patients. This is now prime time on-label first-line therapy for anyone with unresectable and/or metastatic MCC.
The Transplant Conundrum: A patient with a history of organ transplantation over 10 years ago developed unresectable local-regional nodal metastatic MCC. Immunotherapy would typically be the go-to treatment, but the risk of organ transplant failure (30-40%) made it a non-option from the get-go. Instead, the patient underwent chemotherapy to quickly alleviate the symptoms from bulky disease with the possibility of adding concurrent definitive radiotherapy, depending on the PET scan results or ensuring no distant disease. PD1 inhibitors have been used in organ transplant patients with durable responses; however, at the significant risk of graft failure. Certainly, a risk/benefit discussion with the patient if no other alternative options are available. This might be more forgivable in renal transplant patients, where these patients can go back on dialysis. But what to do about lung or liver transplant folks?
The Immunotherapy Refractory Case: A patient resistant to immunotherapy with a single agent may potentially respond by adding CTLA4 inhibitors or considering using intratumoral treatments such as TVEC. There are case series and ongoing clinical trials demonstrating impressive responses to these forms of therapy. The patient I saw had already seen PD1 inhibitors as well as combination PD1/CTLA4 inhibitors and one prior line of chemotherapy. He is otherwise in reasonable shape and not ready to give in to just supportive measures alone. Are there any other newer options to consider? Enter navtemadlin, the new kid on the block, which offers a promising alternative for patients like this one.
Navtemadlin: A New Hope on the Horizon: Navtemadlin is an orally available MDM2 inhibitor designed to restore p53 activity and induce apoptosis of TP53 wild-type tumors. In a phase 1b/2 study (KRT-232-103), patients with TP53 wild-type MCC who failed anti-PD-1/L1 therapy showed a 25% confirmed objective response rate and a 63% disease control rate when receiving 180 mg of navtemadlin on a 5-day on/23-day off schedule. These promising results offer a glimmer of hope for patients who have failed standard immunotherapy treatments. Further enrollment into these protocols either as monotherapy or in combination with immunotherapy are ongoing at many US sites. There are also newer trials using MDNA superkine IL2 and new intratumoral trials using TLR9 agonist concurrent with PD1 inhibitors in the upfront setting.
The battle against Merkel cell carcinoma is far from over, but as we delve into the intricacies of this rare and aggressive skin cancer, innovative treatments like navtemadlin and other novel therapies are offering hope to those who need it most. As we continue our journey, let us remind ourselves that with continued research and dedication, we can make strides towards better outcomes and improved quality of life for those battling MCC.
https://kartosthera.com/science
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
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